Neovascularity also known as angiogenesis is an early feature of inflammatory arthritis disease. Therefore, identifying the development of neovascularity is one way to potentially detect and characterize arthritis. Laser-based photoacoustic imaging (PAI) is an emerging biomedical imaging modality which may aid in detection of both early and continued development of neovascularity. In this work, we investigated the feasibility of PAI to measure angiogenesis, for the purpose of evaluating and monitoring inflammatory arthritis after treatment. The imaging results on an arthritis rat model demonstrate that 1) there is noticeable enhancement in image intensity in the arthritic ankle joints when compared to the normal joints, and 2) there is noticeable decrease in image intensity in the arthritic ankle joints after treatment when compared to the untreated arthritic joints. In order to validate the findings from PAI, we performed positron emission tomography (PET) and histology on the same joints. The diameters of the ankle joints, as a clinical score of the arthritis, were also measured at each time point.
Photoacoustic imaging employing molecular overtone vibration as contrast mechanism opens a new avenue for deep tissue imaging with chemical bond selectivity. Here, we demonstrate vibration-based photoacoustic tomography with an imaging depth on the centimeter scale. To provide sufficient pulse energy at the overtone transition wavelengths, we constructed a compact, barium nitrite crystal-based Raman laser for excitation of 2nd overtone of C-H bond. Using a 5-ns Nd:YAG laser as pumping source, up to 105 mJ pulse energy at 1197 nm was generated. Vibrational photoacoutic spectroscopy and tomography of phantom (polyethylene tube) immersed in whole milk was performed. With a pulse energy of 47 mJ on the milk surface, up to 2.5 cm penetration depth was reached with a signal-to-noise ratio of 12.
A photoacoustic (PA) and ultrasound (US) dual modality system for imaging human peripheral joints is introduced. The system utilizes a commercial US unit for both US control imaging and PA signal acquisition. Preliminary in vivo evaluation of the system on normal volunteers revealed that this system can recover both the structural and functional information of intra- and extra-articular tissues. Presenting both morphological and pathological information in joint, this system holds promise for diagnosis and characterization of inflammatory joint diseases such as rheumatoid arthritis.
Hypoxia is a condition where a region of tissue has less than adequate oxygen. It is of particular importance in tumor biology, as the hypoxic core of tumors has been shown to impede the effectiveness of many therapies. We demonstrate a novel method for oxygen sensing in vivo, based on the photoacoustic lifetime measurement of an oxygen sensitive probe. The experimental results derived from the main artery in the rat tail indicated that the lifetime of the probe, quantified by the photoacoustic measurement, shows a good linear relationship with the blood oxygenation level in the targeted artery.
Identifying neovascularity, i.e. angiogenesis, as a feature of inflammatory arthritis, can help in early diagnosis and treatment monitoring of this disease. Photoacoustic tomography (PAT), as a hybrid imaging modality, relies on intrinsic differences in the optical absorption among the tissues being imaged. Since blood has highly absorbing chromophores including both oxygenated and deoxygenated hemoglobin, PAT holds potential in identifying early angiogenesis associated with inflammatory joint diseases. In this study, we used PAT to identify the changes in the development of inflammatory arthritis, through the study on a well-established adjuvant-induced arthritis (AIA) rat model. Imaging at two different wavelengths, 1064 nm and 532 nm, revealed that there was a significant signal enhancement in the ankle joints of the arthritis affected rats when compared to the normal control group. Histological analysis of both the normal and the arthritic rats correlated well with the imaging findings. The results from this study suggest that the emerging PAT technology could become a new tool for clinical management of inflammatory joint diseases.
A photoacoustic (PA) and ultrasound (US) dual modality system, for imaging human peripheral joints, is introduced. The system utilizes a commercial US unit for both US control imaging and PA signal acquisition. Preliminary in vivo evaluation of the system, on normal volunteers, revealed that this system can recover both the structural and functional information of intra- and extra-articular tissues. Confirmed by the control US images, the system, on the PA mode, can differentiate tendon from surrounding soft tissue based on the endogenous optical contrast. Presenting both morphological and pathological information in joint, this system holds promise for diagnosis and characterization of inflammatory joint diseases such as rheumatoid arthritis.
Identifying neovascularity (angiogenesis) as an early feature of inflammatory arthritis can help in early accurate diagnosis and treatment monitoring of this disease. Photoacoustic tomography (PAT) is a hybrid imaging modality which relies on intrinsic differences in the optical absorption among the tissues being imaged. Since blood has highly absorbing chromophores including both oxygenated and deoxygenated hemoglobin, PAT holds potential in identifying early angiogenesis associated with inflammatory joint diseases. PAT is used to identify changes in the development of inflammatory arthritis in a rat model. Imaging at two different wavelengths, 1064 nm and 532 nm, on rats revealed that there is a significant signal enhancement in the ankle joints of the arthritis affected rats when compared to the normal control group. Histology images obtained from both the normal and the arthritis affected rats correlated well with the PAT findings. Results support the fact that the emerging PAT could become a new tool for clinical management of inflammatory arthritis.
The determination of oxygen levels in blood and other tissues in vivo is critical for ensuring proper body functioning, for monitoring the status of many diseases, such as cancer, and for predicting the efficacy of therapy. Here we demonstrate, for the first time, a lifetime-based photoacoustic technique for the measurement of oxygen in vivo, using an oxygen sensitive dye, enabling real time quantification of blood oxygenation. The results from the main artery in the rat tail indicated that the lifetime of the dye, quantified by the photoacoustic technique, showed a linear relationship with the blood oxygenation levels in the targeted artery.
We successfully encapsulated ICG in an ultrasound-triggerable perfluorocarbon double emulsion that prevents ICG from
binding with plasma proteins. Photoacoustic spectral measurements on point target as well as 2-D photoacoustic images
of blood vessels revealed that the photoacoustic spectrum changes significantly in blood when the ICG-loaded emulsion
undergoes acoustic droplet vaporization (ADV), which is the conversion of liquid droplets into gas bubbles using
ultrasound. Other than providing a new photoacoustic contrast agent, the ICG encapsulated double emulsion, when
imaged with photoacoustic tomography, could facilitate spatial and quantitative monitoring of ultrasound initiated drug
delivery.
Many nanoparticle contrast agents have difficulties with deep tissue and near-bone imaging due to limited penetration of visible photons in the body and mineralized tissues. We are looking into the possibility of mediating this problem while retaining the capabilities of the high spatial resolution associated with optical imaging. As such, the potential combination of emerging photoacoustic imaging and nuclear imaging in monitoring of antirheumatic drug delivery by using a newly developed dual-modality contrast agent is investigated. The contrast agent is composed of gold nanorods (GNRs) conjugated to the tumor necrosis factor (TNF-α) antibody and is subsequently radiolabeled by 125I. ELISA experiments designed to test TNF-α binding are performed to prove the specificity and biological activity of the radiolabeled conjugated contrast agent. Photoacoustic and nuclear imaging are performed to visualize the distribution of GNRs in articular tissues of the rat tail joints in situ. Findings from the two imaging modalities correspond well with each other in all experiments. Our system can image GNRs down to a concentration of 10 pM in biological tissues and with a radioactive label of 5 μCi. This study demonstrates the potential of combining photoacoustic and nuclear imaging modalities through one targeted contrast agent for noninvasive monitoring of drug delivery as well as deep and mineralized tissue imaging.
We have investigated the potential of emerging photoacoustic imaging and nuclear imaging in monitoring of drug
delivery by using a newly developed dual-modality contrast agent. After the contrast agent composed of gold
nanorods (GNRs) was produced, it was radiolabeled by [125I] with high yield and without disturbing the optical
properties of the contrast agent. Photoacoustic and nuclear imaging were conducted to visualize the distribution of
GNRs in articular tissues of rat tail joints in situ. Findings from the two modalities corresponded well with each
other. Using the current imaging systems, GNRs down to a concentration of 10 pM in biological tissues and with a
radioactive label of 5 μCi can be imaged. Moreover, by radiolabeling the GNRs, the in vivo behaviors of the contrast
agent can be monitored conveniently using γ-camera, allowing validation of the findings from emerging
photoacoustic technique. Enabled by the high sensitivity of nuclear imaging, whole-body and longitudinal studies of
the biodistribution of GNRs contrast agent can be performed noninvasively and repeatedly in the same animal. The
highly efficient method reported here provides an extensively useful tool for the guidance of design and
development of new gold nanoparticles as target-specific agents for both diagnostics and therapy.
The characteristic absorption spectrum of hemoglobin depends upon the amount of oxygen the hemoglobin carries. This
property of the hemoglobin enables one to image blood oxygen saturation distribution in biological tissues by using
spectroscopic photoacoustic tomography. In photoacoustic imaging, the amplitude of photoacoustic signal induced by
optical absorption is proportional to light energy deposition which is the product of the optical absorption coefficient and
local light fluence at the imaging target. Since the attenuation of light in biological tissues are wavelength dependent, the
spectrum of local light fluence at a target tissue beneath the sample surface is different from the spectrum of the incident
light fluence above the surface. An unknown spectrum of the light fluence in the sample prevents us from obtaining
quantitative functional images such as oxygen saturation and hemoglobin concentration in the sample by photoacoustic
tomography. We developed a new technique of using an optical contrast agent with known optical absorption spectrum
to obtain the accurate spectrum of light fluence at a subsurface target tissue such as a blood vessel beneath the sample
surface. The technique has been validated by obtaining an accurate absorption spectrum of a micro-flow vessel buried in
strong optical scattering media including diluted whole milk and chicken breast tissue. In this work, we further explored
the capability of this technique through the experiments on tissue mimicking phantoms and living animals. By using this
technique we were able to obtain accurate blood oxygen saturation in vessels buried at different depths in an optical
scattering medium. Also, the oxygenation levels in main arteries in rat tails have been quantified more accurately in a
noninvasive manner.
The photoacoustic technique can be used to quantify tissue absorption spectrum in a wide spectral range from visible to
near infrared. As the photoacoustic signal intensity is proportional to tissue optical absorption coefficient and light
fluence, it is important to know the local light fluence at the regional target in order to obtain the accurate absorption
spectrum because the tissue optical properties including scattering and absorption are wavelength dependent and affect
the distribution and intensity of light in the sample. In this work, an optical contrast agent has been employed to enhance
the performance of spectroscopic photoacoustic technique. From the photoacoustic measurements with and without the
contrast agent in a target tissue, the spectroscopic local light fluence in the tissue can be determined. Then a quantified
measurement of the tissue optical absorption spectrum can be realized in a strong scattering medium without need to
know the wavelength-dependent optical properties in the scattering medium. A commercially available dye which has
strong absorption in the wavelength range of interest was used. The results of the spectroscopic photoacoustic
measurements on fresh canine blood specimens in scattering media such as milk and chicken breast tissue have been
presented. It was found that photoacoustic measurements after employing this new technique have an improved match
with the standard absorption spectra of both oxygenated and deoxygenated blood.
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